Your Guide to ZALTRAP® (ziv-aflibercept)

ZALTRAP (ziv-aflibercept) is a prescription anti-cancer medicine used in combination with the chemotherapy regimen 5-fluorouracil, leucovorin, and irinotecan-(FOLFIRI) to treat metastatic colorectal cancer that has progressed during or after treatment with other anti-cancer medicines that include oxaliplatin.

You or a loved one may be considering therapy with ZALTRAP, also known as ziv-aflibercept, which is an FDA-approved anti-cancer medicine given in combination with a chemotherapy regimen called FOLFIRI (foal-feer-ee) to treat colorectal cancer that has spread. FOLFIRI combines the drugs 5-fluorouracil, leucovorin, and irinotecan. ZALTRAP is an option for people who have had their cancer worsen or have become resistant to the initial therapy used to treat their metastatic colorectal cancer (mCRC).

Those who receive ZALTRAP have been previously treated with a chemotherapy called oxaliplatin (ox-alley-plaht-in).

IMPORTANT SAFETY INFORMATION FOR ZALTRAP® (ziv-aflibercept) INJECTION FOR INTRAVENOUS INFUSION

WARNING: Patients treated with ZALTRAP have experienced serious and sometimes fatal side effects.
Your doctor may adjust or stop your ZALTRAP treatment if you have these or other side effects.
Tell your doctor right away if you experience any of the following:

Severe bleeding. ZALTRAP can cause severe internal bleeding including bleeding of the digestive
system, brain, or lungs. Signs and symptoms may include blood in the stool or urine,
abdominal pain or lightheadedness. Patients with severe bleeding should not take ZALTRAP.

Gastrointestinal perforation. ZALTRAP can also cause a hole in the stomach, esophagus, or intestines.
Symptoms may include abdominal pain, vomiting, fever, and chills.

Wounds that don’t heal. ZALTRAP can interfere with wound healing. Do not undergo surgery or medical procedures
(including tooth extractions) without discussing first with your doctors, as ZALTRAP should not be used at least
4 weeks before or 4 weeks after surgery and until the wound is fully healed.

Patients treated with ZALTRAP have experienced serious side effects. Your doctor may adjust or stop your ZALTRAP treatment if you have these or other side effects:

A fistula could form in your body. This is an abnormal passage that forms from one part of the body to another.

Hypertension (high blood pressure) may develop or get worse. In clinical trials, about half of patients treated with ZALTRAP who developed high blood pressure requiring treatment developed it within the first 2 cycles of ZALTRAP treatment. Your doctor will monitor your blood pressure regularly during treatment. Take anti-hypertensive therapy as directed by your doctor. Signs of high blood pressure may include severe headache, lightheadedness, confusion or similar neurological disorders.

Arterial Thromboembolic Events (Blood clots that form in arteries). Blood clots can form and travel to the brain and cause a stroke or to the heart and cause severe chest pain or other heart damage.

Too much protein in the urine (proteinuria). This may be a sign of kidney damage. Your doctor will monitor your urine protein levels during treatment. Signs of severe proteinuria may include swelling of the feet, hands, face, or abdomen.

Low white blood cell count. This could lead to serious infections. Your doctor will monitor your white blood cell count regularly during treatment. Fever may be a sign of low white blood cell count and serious infection. Check your temperature regularly during treatment and tell your doctor if you have a fever.

Severe diarrhea and dehydration. Severe diarrhea can occur, especially in patients 65 years of age and older. Severe diarrhea (including vomiting) takes fluids from the body and can lead to dehydration.

RPLS (Reversible Posterior Leukoencephalopathy Syndrome). This is a very rare but serious brain disorder. Signs and symptoms include headache, seizures, visual changes, and changes in mental function. These symptoms usually stop or improve within days, but some patients experienced continuing changes in mental function or death.

Before receiving ZALTRAP, tell your doctor if you:

have had bleeding problems, blood clotting problems, or are taking blood thinners (called warfarin [Coumadin®] or heparin) for the treatment of blood clots

are or have recently been coughing up blood

have gastrointestinal problems such as gastric ulcers or diverticulitis, or history of prior perforation of the intestine

have had a tooth extracted or any other surgery within the last 4 weeks, if you have a surgical wound that has not healed, or if you are going to have an operation or a dental or medical procedure

have high blood pressure

have heart or circulation problems, or history of stroke

have kidney problems

have history of seizures

are allergic to or have had a reaction to any medicine

had recent treatments for cancer that your doctor is not aware of

are pregnant or plan to become pregnant. ZALTRAP may harm your unborn baby. You should not become pregnant while receiving ZALTRAP therapy. Both men and women should use highly effective contraception during and for at least 3 months following the last dose of ZALTRAP. Tell your doctor right away if you become pregnant or are concerned that you have become pregnant while receiving ZALTRAP

are breastfeeding or plan to breastfeed. It is not known if ZALTRAP passes into your breast milk. You should not breastfeed while receiving ZALTRAP therapy

The most common side effects of ZALTRAP include:

Low white blood cell count (neutropenia)

Diarrhea

Too much protein in the urine

Increase in liver enzymes

Painful sores in the mouth

Feeling tired and weak

Low blood platelet count. Tell your doctor if you have any unusual bruising or bleeding

Increased blood pressure

Increased blood pressure

Decreased appetite

Nose bleed

Stomach (abdominal) pain

Change in voice (hoarseness)

Changes in kidney function

Headache

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of ZALTRAP. For more information, ask your doctor or pharmacist. You may report side effects to FDA at 1-800-FDA-1088.